González-Mariscal L, Betanzos A, Nava P, Jaramillo B E
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), Ave. Politécnico Nacional 2508, México DF, 07000, Mexico.
Prog Biophys Mol Biol. 2003 Jan;81(1):1-44. doi: 10.1016/s0079-6107(02)00037-8.
A fundamental function of epithelia and endothelia is to separate different compartments within the organism and to regulate the exchange of substances between them. The tight junction (TJ) constitutes the barrier both to the passage of ions and molecules through the paracellular pathway and to the movement of proteins and lipids between the apical and the basolateral domains of the plasma membrane. In recent years more than 40 different proteins have been discovered to be located at the TJs of epithelia, endothelia and myelinated cells. This unprecedented expansion of information has changed our view of TJs from merely a paracellular barrier to a complex structure involved in signaling cascades that control cell growth and differentiation. Both cortical and transmembrane proteins integrate TJs. Among the former are scaffolding proteins containing PDZ domains, tumor suppressors, transcription factors and proteins involved in vesicle transport. To date two components of the TJ filaments have been identified: occludin and claudin. The latter is a protein family with more than 20 members. Both occludin and claudins are integral proteins capable of interacting adhesively with complementary molecules on adjacent cells and of co-polymerizing laterally. These advancements in the knowledge of the molecular structure of TJ support previous physiological models that exhibited TJ as dynamic structures that present distinct permeability and morphological characteristics in different tissues and in response to changing natural, pathological or experimental conditions.
上皮细胞和内皮细胞的一项基本功能是分隔生物体内的不同腔室，并调节它们之间的物质交换。紧密连接（TJ）对离子和分子通过细胞旁途径的通透以及蛋白质和脂质在质膜顶端和基底外侧结构域之间的移动均构成屏障。近年来，已发现40多种不同的蛋白质定位于上皮细胞、内皮细胞和有髓鞘细胞的紧密连接处。这一前所未有的信息扩展改变了我们对紧密连接的看法，从仅仅是一个细胞旁屏障转变为参与控制细胞生长和分化的信号级联反应的复杂结构。皮质蛋白和跨膜蛋白都整合到紧密连接中。前者包括含有PDZ结构域的支架蛋白、肿瘤抑制因子、转录因子以及参与囊泡运输的蛋白质。迄今为止，已鉴定出紧密连接丝的两个成分：闭合蛋白和Claudin蛋白。后者是一个有20多个成员的蛋白质家族。闭合蛋白和Claudin蛋白都是整合蛋白，能够与相邻细胞上的互补分子进行粘附性相互作用，并能在侧向共聚。紧密连接分子结构知识的这些进展支持了以前的生理学模型，该模型将紧密连接展示为动态结构，在不同组织中以及响应不断变化的自然、病理或实验条件时呈现出不同的通透性和形态特征。
